HIF-1 alpha is required for development of the sympathetic nervous system

0507766 - BTÚ 2020 RIV US eng J - Journal Article
Bohuslavová, Romana - Čerychová, Radka - Papoušek, František - Olejníčková, Veronika - Bartoš, M. - Goerlach, A. - Kolář, František - Sedmera, David - Semenza, G.L. - Pavlínková, Gabriela
HIF-1 alpha is required for development of the sympathetic nervous system.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 116, č. 27 (2019), s. 13414-13423. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA ČR GA17-04719S; GA ČR(CZ) GA19-07378S; GA MŠMT(CZ) LTC17023; GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) ED1.1.00/02.0109
Research Infrastructure: Czech-BioImaging - 90062
Institutional support: RVO:86652036 ; RVO:67985823
Keywords : sympathetic neurons * tyrosine hydroxylase * cardiac innervation
OECD category: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (FGU-C)
Impact factor: 9.412, year: 2019
Method of publishing: Open access
https://doi.org/10.1073/pnas.1903510116

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1 alpha (HIF-1 alpha) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1 alpha impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1 alpha for development of the sympathetic nervous system.
Permanent Link: http://hdl.handle.net/11104/0298742